There is compelling evidence for the involvement of the hippocampus in certain forms of information storage. Part of this ability may be accounted for by use-dependent plasticity of excitatory synaptic connections in the hippocampus-one of these being called long-term potentiation. Another, less-appreciated feature of the hippocampus that may contribute to information storage and processing is the extensive network of recurrent excitatory synapses among CA3 pyramidal neurons. These synapses could provide a substrate for auto-associative memory. Understanding the functional properties of recurrent (and other) synapses in CA3 is a necessary prerequisite for understanding how information is processed in the hippocampus under both normal conditions and under the pathological conditions known to involve the hippocampus; e.g. temporal lobe epilepsy, Alzheimer's disease, and schizophrenia. We propose to investigate two poorly understood synaptic inputs to CA3: the recurrent synapses among CA3 neurons and the perforant path (PP) synapses from the entorhinal cortex. One underlying theme of this project is that the active and passive membrane properties of the dendrites modify (and thus process) synaptic inputs in ways dependent on the location of the synapses in the dendrites and the activity of other synapses. A major focus of our experimental studies will therefore be an investigation of the dendritic mechanisms (e.g. calcium influx and membrane potential) that contribute towards the various forms of synaptic plasticity observed in CA3. The electrotonic distances of the synapses from the soma present severe technical difficulties for traditional electrophysiological recording methods. We will overcome this problem by combining modem electrophysiological and fluorescent imaging techniques with experiments in rat hippocampal slices. We will then use these data in conjunction with realistic computer models of CA3 pyramidal neurons to test predictions derived from our experiments and to explore various theories of cellular information processing in hippocampus. We will examine these questions: 1) What axe the physiological properties of recurrent and PP synapses in CA3? 2) What are the induction rules for homosynaptic, heterosynaptic, and associative plasticity of synaptic inputs to CA3? 3) What are the changes in calcium influx and membrane potential in the dendrites during synaptic activity? 4) How do dendrites of CA3 neurons integrate and modify incoming synaptic inputs and how do active synapses communicate with other active (and inactive) synapses in the dendrites?